The present invention is directed to an improved electrolytic cell having novel electrolytes and/or novel electrode materials. The electrolytic cell can be used as a gas generator for a drug delivery device.
There are many applications requiring the dispensing or delivering of a liquid at a predetermined or precisely controlled rate. One application requiring a particularly precise rate of delivery is a system for administering a drug, such as insulin or morphine. Precise pumps have been devised for this purpose. However, such pumps are expensive to produce and maintain, and are inconvenient to refill with the periodic dosage requirements.
One solution to this problem is to use an electrolytic cell as a gas generator which functions to dispense a liquid from a device. For example, U.S. Pat. No. 5,062,834 (xe2x80x9cthe ""834 patentxe2x80x9d), for xe2x80x9cDevice for Dispensing a Liquid Particularly Useful for Delivering Medicaments at a Predetermined Rate,xe2x80x9d describes a device for dispensing a liquid at a predetermined rate. The device comprises a container for the liquid to be dispensed and a piston assembly movable within the container and dividing the container into two expandable-contractible chambers. The first chamber contains the liquid to be dispensed and the second chamber contains pressurized gas which functions to dispense the liquid from the first chamber of the container. The second expandable-contractible chamber includes an electrolytic cell having electrodes and an electrolyte. Upon energization of the cell, the electrolyte conducts current between the electrodes, triggering the generation of gas.
The electrolytic cell of the ""834 patent comprises a pair of electrodes and an electrolyte capable of generating a gas upon energization of the electrodes. The gas expands the second chamber which results in displacing a piston, thereby forcing the liquid out from the first chamber. Examples of useful electrolytes include saline solution and other polar solutions or gels which generate hydrogen, oxygen, nitrogen or carbon dioxide. A similar device containing an electrolytic cell is described in U.S. Pat. No. 5,242,406 for xe2x80x9cLiquid Delivery Device Particularly Useful for Delivering Drugs.xe2x80x9d
Another example of an electrolytic cell used in a drug delivery device is given in U.S. Pat. No. 5,090,963 for xe2x80x9cElectrochemically Driven Metering Medicament Dispenser.xe2x80x9d This patent describes a liquid material dispenser comprising an electrolytic cell capable of generating a gas when energized by a source of electric current. The liquid material dispenser comprises a rigid housing having a flexible partition forming two compartments. Upon energization by a source of electric current, the electrolytic cell in the first compartment generates a gas, thereby expanding the first compartment of the dispenser. This results in contracting the second compartment containing the liquid material, thereby dispensing the liquid material. The patent teaches that the electrolyte can be an 8% solution of sodium bicarbonate (NaHCO3) in water or a 4% solution of copper sulphate (CuSO4) in water.
Yet another example of a prior art use of an electrolytic cell in a drug delivery device is given in U.S. Pat. No. 5,186,805 (xe2x80x9cthe 805 patentxe2x80x9d) for xe2x80x9cElectrolytic Dispensing Device.xe2x80x9d This patent describes a device similar to that the ""834 patent. For this particular adaptation of an electrolytic cell, the electrodes are preferably stainless steel nets or screens. The electrolyte can be a water solution of various salts or acids, such as baking soda (sodium bicarbonate), caustic soda, magnesium sulphate, potassium sulphate, sodium sulphate, potassium nitrate, potassium bicarbonate, boric acid, acetic acid, formic acid, or carbonic acid. The ""805 patent teaches that particularly good results were obtained using an 8% solution of baking soda (sodium bicarbonate) as an electrolyte.
Finally, a liquid material dispenser, in which the liquid is forced from the dispenser by a gas generated by an electrolytic cell, is described in U.S. Pat. No. 5,704,520. The electrolytic cell contains electrodes and electrolyte. Suitable electrolytes are disclosed to be sodium bicarbonate and potassium acetate.
While these prior art references describe useful electrolytic cells, there remains a need in the art for improved electrolytic cells useful in drug delivery devices. In particular, there is a need for electrolytic cells having a more constant rate of gas production and electrolytic cells having a controlled variable rate of gas production. The present invention satisfies these needs.
The present invention is directed to an improved electrolytic cell having a new electrolyte and/or a new electrode composition for water electrolysis or other type of electrochemical reaction. The invention also encompasses pre-treatment protocols for electrodes which produce a more efficient electrolytic cell. The electrolytic cell is useful as a gas generator in a drug delivery device.
The improved cell allows for miniaturization of the electrolytic cell and any device incorporating such a cell. The novel electrolytic cell is one of the smallest electrolytic cells comprising a liquid electrolyte. The miniaturization or micronization is possible because the cell delivers a large amount of gas volume as compared to the size and quantity of components. The miniaturized electrolytic cell can be used in human applications, such as for administering drugs to be applied either externally or internally. In addition to being useful on a small scale, the electrolytic cell of the invention can be scaled-up and used in commercial manufacturing settings.
In a first embodiment, the improved electrolytic cell exhibits a constant rate of gas production over a prolonged period of time. For this type of cell, the anode must be insoluble in an anodic dissolution process, which is an electrochemical reaction (this is distinguishable from chemical or other types of dissolution); the cathode can be chosen from a wide variety of materials. Steady state production over an extended period of time, as shown below, is highly desirable as such a constant rate produces a constant rate of drug delivery when the electrolytic cell is employed in a drug delivery device. 
In a second embodiment, the electrolytic cell can be designed to have a controlled variable rate of gas production, as shown below. For this type of cell, the anode is soluble, such as brass or copper. Such a variable rate is desirable for certain types of applications, such as delivering pain medication, in which it is preferred that an initial high delivery rate is followed by a lower constant rate. 
In a third embodiment, the electrolytic cell is designed to have an pulsatile rate of gas production, as shown below. For this type of cell, the anode is insoluble material in an anodic dissolution process, which is an electrochemical reaction (this is distinguishable from chemical or other types of dissolution); the cathode can be chosen from a wide variety of materials. Such an intermittent rate of gas production is useful for certain types of applications, such as for irrigation systems, for the addition of fertility materials to irrigation water, and for administering insulin or hormones to mammals. 
An electrolytic cell of the invention is dramatically superior to prior art cells in that it is simple and cost effective to manufacture, it is composed of materials that are safe and non-toxic, and it can be used in a variety of applications. For example, an electrolytic cell according to the invention can be used in a drug delivery device to administer a steady and controlled amount of drug over an extended period of time. Alternatively, the an electrolytic cell according to the invention can be used to administer a high amount of medication immediately following use, followed by a lower steady rate of administration, or the electrolytic cell can be used to administer a drug at intermittent periods of time.
A. New Electrolyte
The new electrolyte and/or electrode composition are useful in an electrolytic cell comprising the electrolyte and at least two electrodes (anode and cathode) connected to an external source of electrical current, such as a battery, for generating gas. In use, the electrolyte conducts electrical current between the electrodes and, as a result of an electrochemical reaction, gas is generated. The rate of gas production corresponds to the electrical current supplied to the electrolytic cell, and the total amount of gas produced is related to the electrical current supplied to the cell during the time of operation.
The new electrolyte is di-potassium hydrogen phosphate solution, K2HPO4. Less alkaline phosphate buffer (i.e., K2HPO4+KH2PO4) may also be used as an electrolyte. The preferred pH of the electrolyte is about 8.0 to about 11.0, and the preferred concentration of the electrolyte is from about 1 to about 6 M. For example, the pH of 5.50-5.55 M K2HPO4 solution is 10.5 to 11.0. The pH of the solution can be reduced to any desired value, such as reducing the pH from 11.0 to 8.0, by adding a proper amount of phosphoric acid of the same molarity. Such a method does not change the concentration of the electrolyte solution.
With the use of a low level of current, i.e., less than about 2 mA, the electrolyte is preferably present at a concentration of about 5.50 to 5.55 M. With the use of a high level of current, i.e., greater than 7 mA, the concentration of the electrolyte is preferably from about 1 M to about 2 M. The new electrolyte is inexpensive, non-toxic, safe, and simple to produce.
An electrochemical gas generator having the new electrolyte delivers gas for an extended period of time. The presence of reactants in suitable amounts and the volume of electrolyte solution are two of the factors which determine the life of the electrolytic cell. Thus, large scale electrolytic cells can operate for years as long as a sufficient quantity of electrolyte solution is present in the cell. The practical limitation of the life span of a micronized or miniaturized cell is the time it takes the electrolyte solution to dry. This is because the electrochemical reaction consumes a relatively negligible amount of water compared with the volume of gas produced. Thus, if water is added to the cell it can be re-used almost indefinitely.
The new electrolyte can be used in any water-electrolysis based electrolytic cell operating at low currents, as well as other types of electrolytic cells operating at high or low currents. The cells can be used, for example, in drug delivery devices, such as those described in U.S. Pat. Nos. 5,242,406; 5,062,834; 5,704,520; 5,090,963; and 5,186,805, which are specifically incorporated by reference.
A drug delivery device incorporating the new electrolyte can be used, for example, in low-cost disposable devices for one-time use and in devices that may be fixed to a band or strap for attachment to the body, e.g., the arm, of the person to receive the medicament dispensed from the device.
B. Electrode Composition
Yet another aspect of the invention is directed to the use of various materials for the electrode. Modification of electrode materials can result in a modification of the rate of gas production, which can thereby control the rate of a substance being delivered. Preferred anode compositions for producing a steady rate or pulsatile rate of gas production are certain noble metals, stainless steel, and nickel. Useful noble metals are, for example, platinum, iridium, rhodium, ruthenium, osmium, and alloys thereof. Gold, or alloys thereof, can also be used, although gold is not preferred because it can cause high overvoltage. Alloys of noble metals for use in anodes of electrolytic cells having steady rate or pulsatile rate of gas production do not contain metals which are soluble in an electrochemical reaction. Stainless steel is preferred as it is inexpensive. Preferred anode compositions for producing an initial high rate of gas production, followed by a lower steady rate of gas production, are brass and copper. Cathode compositions for all three types of gas rate production (steady state, pulsatile, and controlled variable) can be selected from a wide range of materials.
The anode and cathode for all three types of applications can be made of the same or different materials. If the shelf life of the electrolytic cell is to be short, then different materials can be used for the anode and cathode compositions. However, if the shelf life of the electrolytic cell is to be long, then it is preferred that the anode and cathode are made of the same material to avoid potential corrosion during storage.
A device having an electrolytic cell and controlled changes in gas evolution can be used, for example, for pain treatment. Such a device could be used for the delivery of morphine. At initiation, a patient requiring pain treatment requires a high rate of drug delivery. After the initial treatment period, however, the rate of drug delivery must decay. With the use of an electrolytic pump having controlled changes in gas evolution, a drug delivery device can provide a high rate of initial delivery followed by a steady lower rate of delivery. Such a drug delivery device is dramatically superior to prior art delivery devices, as it does not require smart electronics or any other complicated mechanism, and therefore, is simple, efficient, and cost-effective.
C. Treatment Protocol for Electrode Surface
One of the critical parameters of an electrochemical reaction is the initial condition of the electrode surface area. If the electrode surface area is clean and free of an organic or other film or adsorbed species, it is active and electrochemical reactions using the electrode will have high current efficiency.
There are many different methods of pre-treating electrode surfaces, such as mechanical, thermal, chemical, and electrochemical treatments. The method chosen depends upon the intended use of the cell, the electrode design, the nature of the electrolyte, and the cell design. One popular chemical pretreatment method for platinum electrodes uses a xe2x80x9cpiranhaxe2x80x9d solution, consisting of a mixture of sulfuric acid and hydrogen peroxide.
For use of the electrolytic cell of the invention in a miniaturized form at low currents, the initial electrode surface is significant as the efficiency of gas delivery is critical. If the electrode surface in such a device was not pretreated, the gas evolution of the device may be unstable (i.e., a non-linear drug delivery curve), the drug delivery may be initially delayed because the current would have to penetrate the electrode surface film, and the repeatability of the results would be poor because the initial electrode surface would not be controlled. This is most significant for drug devices, as regulatory approval of such devices requires that results are repeatable and consistent.
The pretreatment process of the invention comprises pretreating stainless steel, copper, or brass electrodes by washing with ethyl alcohol and rinsing, dipping the electrodes in citric acid and rinsing, followed by activating the electrodes with the electrolyte. A pretreatment process for nickel electrodes is also disclosed.
Both the foregoing general description and the following detailed description are exemplary and explanatory and are intended to provide further explanation of the invention as claimed. Other objects, advantages, and novel features will be readily apparent to those skilled in the art from the following detailed description of the invention.